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目的比较HPV16型E7抗原CTL表位E711-20(YMLDLQPETT)与其修饰多肽配体APL(YLLDLQPE-VT)诱发特异CTL免疫应答的能力和抗肿瘤免疫治疗的作用。观察E711-20及其APL的小鼠TC-1细胞肿瘤免除率、存活时间与荷瘤小鼠的肿瘤体积变化,了解其预防和治疗效果。方法以E711-20及其修饰多肽配体(APL)免疫C57BL/6小鼠,测定免疫后小鼠脾淋巴细胞的增殖指数;用LDH释放试验检测免疫后小鼠脾淋巴细胞的CTL杀伤活性。结果脾细胞增殖实验中,3组增殖指数如下:IFA+APL组2.42±0.38,IFA+E711-20组1.68±0.32,IFA组1.07±0.22;CTL杀伤效应实验中,3组靶细胞溶破率(%)如下:IFA+APL组54.21±0.12,IFA+E711-20组62.33±0.46,IFA组0.88±0.07;IFA组肿瘤免除率为0,IFA+E711-20组肿瘤免除率为40%,IFA+APL组肿瘤免除率为80%;荷瘤小鼠中,对照组IFA肿瘤体积迅速增大,E711-20和APL组的肿瘤生长速度较慢。APL免疫诱导的小鼠脾淋巴细胞,其CTL杀伤活性和增殖能力强于E711-20;APL对TC-1肿瘤细胞的预防和治疗效果优于E711-20。结论 APL诱导特异性抗肿瘤免疫应答的能力和抗肿瘤效果优于E711-20,可能为针对HPV16E7抗原的肽疫苗分子设计提供理想的CTL表位。
Objective To compare the ability of CTL epitope E711-20 (YMLDLQPETT) and its modified peptide ligand APL (YLLDLQPE-VT) to induce specific CTL immune responses and the anti-tumor immunotherapy of HPV16 E7 antigen. Observe the E711-20 and its APL mouse TC-1 cell tumor-free rate, survival time and tumor-bearing mice tumor volume changes, to understand the prevention and treatment effect. Methods C57BL / 6 mice were immunized with E711-20 and its modified polypeptide ligand (APL) to measure the proliferation index of splenic lymphocytes. The LDH release assay was used to detect the CTL activity of splenic lymphocytes. Results In the splenocyte proliferation test, the proliferative index of the three groups were as follows: 2.42 ± 0.38 in IFA + APL group, 1.68 ± 0.32 in IFA + E711-20 group and 1.07 ± 0.22 in IFA group. In the CTL killing effect experiment, (IFA + E711-20 group, 62.33 ± 0.46, IFA group, 0.88 ± 0.07); IFA group tumor rejection rate was 0, IFA + E711-20 group tumor rejection rate was 40% In tumor-bearing mice, the tumor volume of IFA + APL group increased rapidly and the tumor volume of IFA + APL group increased rapidly. The tumor growth rate was slower in E711-20 and APL groups. APL immune-induced mouse splenic lymphocytes, its CTL cytotoxicity and proliferation ability than E711-20; APL TC-1 tumor cell prevention and treatment effect is better than E711-20. Conclusions APL is superior to E711-20 in inducing specific anti-tumor immune response and anti-tumor effect, which may provide an ideal CTL epitope for peptide vaccine molecule design targeting HPV16 E7 antigen.